TF and its down-stream product thrombin have been shown to contribute to the inflammatory-related pathogenesis of myocardial necrosis secondary to ischemia-reperfusion. This application tests the overall hypothesis that the tissue factor complex and thrombin stimulate an inflammatory response to cardiopulmonary bypass, cardiac arrest (cardioplegia) and reperfusion. Studies will test the following aims: Aim 1: Determine the time course of TF-thrombin pathway expression and endothelial activation during cardiopulmonary bypass, and after cardioplegic arrest and reperfusion in myocardium and other tissues. Aim 2: Determine a functional link between TF-thrombin pathway and activation of the vascular endothelium and inflammatory responses. Aim 3: Determine if inhibition of the TF-thrombin pathway improves physiological outcomes after cardiopulmonary bypass, cardioplegic arrest and reperfusion. These studies will lead to an understanding of a potentially new mechanism in the inflammatory response to surgical ischemia-reperfusion and cardiopulmonary bypass.